A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS

By L. Dai, Tianyi Zheng, Kun Xu, Yuxuan Han, Lili Xu, E. Huang, Yaling An, Yin-Hong Cheng, Shihua Li, Mei Liu and 11 more. 2020

461 citations recorded by the source corpus.

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

Subfields: Infectious Diseases

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “…with a recent report of dimerization increasing the immunogenicity of the RBD from several coronavirus S proteins, including SARS-CoV-2 S (Dai et al., 2020), as well as a nanoparticle vaccine candidate for Epstein-Barr virus conceptually similar to our RBD nanoparticle immunogens that…”